Antihistamines find wide use in treating allergies by blocking the binding of histamine to histamine H1-receptors and thereby suppressing symptoms such as a runny nose or watery eyes. So-called first generation antihistamines were developed that provided excellent reduction in the symptoms of rhinitis, however many of these early compounds induced a sedative effect in the patient, as they are nonselective for the H1-receptor. Depending upon the time of day of administering a conventional recommended dose of a first generation antihistamine, the sedative effect may or may not be desired. For example, sedation would not be desired during the day while most patients need to be active and fully functional, often requiring awareness for daily activities such as working or driving a car.
Second and third generation antihistamines were subsequently designed to avoid the sedative effect exhibited in the earlier generation of compounds. These compounds were developed such that they do not cross the blood brain barrier and thus are selective for peripheral H1 receptors outside of the central nervous system, thereby exhibiting a reduced sedative effect.
Although the second and third generation antihistamines avoid the sedative effect of the first generation antihistamines, they exhibit a lag from the time of administration to time when the patient starts to experience symptomatic relief. Several second generation antihistamines, such as terfenadine, astemizole, cetirizine, and loratadine, exhibit a lag time of several hours before onset of action (See Annals of Allergy, Asthma, & Immunology (1997), 79, 163-172).
Thus, there remains a need in the art for methods of administering antihistamines that provides rapid, sustained, and improved therapeutic effect while at the same time avoiding a sedative effect such that the administration can occur regardless of the time of day.